Physical interactions between MCM and Rad51 facilitate replication fork lesion bypass and ssDNA gap filling by non-recombinogenic functions

The minichromosome maintenance (MCM) helicase physically interacts with the recombination proteins Rad51 and Rad52 from yeast to human cells. We show, in Saccharomyces cerevisiae, that these interactions occur within a nuclease-insoluble scaffold enriched in replication/repair factors. Rad51 accumul...

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Detalhes bibliográficos
Autores: Cabello-Lobato, María J., González-Garrido, Cristina, Cano-Linares, María I., Wong, Ronald P., Yáñez-Vilches, Aurora, Morillo-Huesca, Macarena, Roldán-Romero, Juan M., Vicioso Mantis, Marta, González-Prieto, Román, Ulrich, Helle D., Prado, Félix
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/259672
Acesso em linha:http://hdl.handle.net/10261/259672
Access Level:Acceso aberto
Palavra-chave:DNA damage
MCM
Rad51
Rad52
Cdc7
Homologous recombination
Replication
Descrição
Resumo:The minichromosome maintenance (MCM) helicase physically interacts with the recombination proteins Rad51 and Rad52 from yeast to human cells. We show, in Saccharomyces cerevisiae, that these interactions occur within a nuclease-insoluble scaffold enriched in replication/repair factors. Rad51 accumulates in a MCM- and DNA-binding-independent manner and interacts with MCM helicases located outside of the replication origins and forks. MCM, Rad51, and Rad52 accumulate in this scaffold in G1 and are released during the S phase. In the presence of replication-blocking lesions, Cdc7 prevents their release from the scaffold, thus maintaining the interactions. We identify a rad51 mutant that is impaired in its ability to bind to MCM but not to the scaffold. This mutant is proficient in recombination but partially defective in single-stranded DNA (ssDNA) gap filling and replication fork progression through damaged DNA. Therefore, cells accumulate MCM/Rad51/Rad52 complexes at specific nuclear scaffolds in G1 to assist stressed forks through non-recombinogenic functions.

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